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Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease

An Erratum to this article was published on 01 June 2004

Abstract

Skin is the most commonly affected organ in graft-versus-host disease (GVHD). To explore the role of Langerhans cells in GVHD, the principal dendritic cells of the skin, we studied the fate of these cells in mice transplanted with allogeneic bone marrow. In contrast to other dendritic cells, host Langerhans cells were replaced by donor Langerhans cells only when donor T cells were administered along with bone marrow, and the extent of Langerhans cell chimerism correlated with the dose of donor T cells injected. Donor T cells depleted host Langerhans cells through a Fas-dependent pathway and induced the production in skin of CCL20, which was required for the recruitment of donor Langerhans cells. Administration of donor T cells to bone marrow–chimeric mice with persistent host Langerhans cells, but not to mice whose Langerhans cells had been replaced, resulted in marked skin GVHD. These findings indicate a crucial role for donor T cells in host Langerhans cell replacement, and show that host dendritic cells can persist in nonlymphoid tissue for the duration of an animal's life and can trigger GVHD despite complete blood chimerism.

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Figure 1: Host Langerhans cells (LCs) persist in the skin after allogeneic stem cell transplantation.
Figure 2: Allogeneic T cells deplete host Langerhans cells (LCs) through a Fas ligand–dependent pathway.
Figure 3: Expression of CCR2 and CCR6 on donor bone marrow (BM) cells is required for Langerhans cell (LC) chimerism.
Figure 4: Host Langerhans cells (LCs) that persist in chimeric mice induce severe skin GVHD.
Figure 5: Depletion of host Langerhans cells (LCs) prevents skin GVHD.

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Acknowledgements

E.G.E. was funded by grant HL57443 from the National Institutes of Health (National Heart, Lung and Blood Institute). S.A.L. is an Irene Diamond Associate Professor in Immunology.

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Correspondence to Miriam Merad.

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Merad, M., Hoffmann, P., Ranheim, E. et al. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nat Med 10, 510–517 (2004). https://doi.org/10.1038/nm1038

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